Mammary Gland Cell Death Also Involves Lysosomal Autophagy

The mammary gland undergoes apoptosis when estrogen ablation occurs, either naturally or enforced. The gland is known to execute the apoptotic process post weaning. Although the involuting mammary gland displays the characteristic biochemical features of apoptosis, including DNA fragmentation, chromatin condensation, and the formation of apoptotic bodies, it also shows evidence of an autophagic death. In this report, apoptosis of the gland was induced by removing the pups from their nursing mothers. In particular, we show that lysosomes increased in size and number, and moved from basal to apical regions in dying rat mammary gland cells. Lysosomal enzyme activities were significantly greater in degenerating mammary gland (day 4 post weaning) epithelial cells when compared with day 0 gland cells. Moreover, these hydrolases were responsible for degrading cytosolic and nuclear components, and thus the whole cell. Taken together, our results demonstrate that the mammary gland dies by lysosomal autophagy in addition to apoptosis during post-lactational involution. Our studies indicate that the lysosomal compartment may serve as an important target organelle for the creation of specific, effective, and novel therapies for breast cancer.